ITM2C

integral membrane protein 2C, the group of BRICHOS domain containing

Basic information

Region (hg38): 2:230864639-230879248

Links

ENSG00000135916 ∙ NCBI:81618 ∙ OMIM:609554 ∙ HGNC:6175 ∙ Uniprot:Q9NQX7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITM2C gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITM2C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			18			18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	0	2

Variants in ITM2C

This is a list of pathogenic ClinVar variants found in the ITM2C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-230865053-G-T		not specified	Uncertain significance (Dec 01, 2022)
2-230865098-G-A		not specified	Uncertain significance (Mar 25, 2024)
2-230865108-C-T		not specified	Uncertain significance (Jul 12, 2022)
2-230873448-G-C		not specified	Uncertain significance (Mar 29, 2023)
2-230873449-G-C		not specified	Uncertain significance (Oct 05, 2023)
2-230873465-G-A		not specified	Uncertain significance (Feb 15, 2023)
2-230873504-A-G		not specified	Uncertain significance (Sep 22, 2022)
2-230873516-T-A		not specified	Uncertain significance (May 28, 2024)
2-230875627-G-A		not specified	Uncertain significance (Oct 12, 2021)
2-230875642-G-A		not specified	Likely benign (Mar 30, 2024)
2-230876881-T-A		not specified	Uncertain significance (Apr 05, 2023)
2-230876897-A-G		not specified	Uncertain significance (Apr 04, 2023)
2-230876936-G-A		not specified	Uncertain significance (Jan 16, 2024)
2-230876962-G-A		not specified	Uncertain significance (Feb 22, 2023)
2-230877400-A-T		not specified	Uncertain significance (Aug 28, 2023)
2-230877483-G-T			Benign (Dec 28, 2017)
2-230877499-C-T			Benign (Apr 17, 2018)
2-230877505-A-T		not specified	Uncertain significance (Nov 21, 2023)
2-230877530-G-A		not specified	Uncertain significance (Oct 03, 2022)
2-230877533-G-A		not specified	Uncertain significance (Aug 16, 2022)
2-230877535-C-T		not specified	Uncertain significance (Jan 30, 2024)
2-230877544-C-T		not specified	Uncertain significance (Aug 16, 2021)
2-230878017-A-G		not specified	Uncertain significance (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITM2C	protein_coding	protein_coding	ENST00000326427	6	14610

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.704	0.295	125731	0	10	125741	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.380	159	173	0.919	0.0000116	1722
Missense in Polyphen		40	59.234	0.67528		656
Synonymous	-0.282	77	73.9	1.04	0.00000508	534
Loss of Function	2.78	2	12.7	0.158	7.24e-7	137

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000447	0.0000439
Middle Eastern	0.000218	0.000217
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of amyloid-beta peptide production. May inhibit the processing of APP by blocking its access to alpha- and beta-secretase. Binding to the beta-secretase-cleaved APP C-terminal fragment is negligible, suggesting that ITM2C is a poor gamma-secretase cleavage inhibitor. May play a role in TNF- induced cell death and neuronal differentiation (By similarity). {ECO:0000250, ECO:0000269|PubMed:18452648, ECO:0000269|PubMed:19366692}.

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.711
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.211
• hipred: Y
• hipred_score: 0.687
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.641

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Itm2c
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of neuron projection development;neuron differentiation;negative regulation of amyloid precursor protein biosynthetic process;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: lysosome;lysosomal membrane;Golgi apparatus;plasma membrane;integral component of membrane;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: amyloid-beta binding;protein binding;ATP binding